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Long noncoding RNA NEAT1 is an unfavorable prognostic factor and regulates migration and invasion in gastric cancer

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Long noncoding RNAs (LncRNAs) have been demonstrated as playing important roles in diverse biological processes including tumorigenesis. However, the clinical significance and biological function of LncRNA nuclear-enriched abundant transcript 1 (NEAT1) in gastric cancer are still unknown. The aim of this study was to identify the role of LncRNA NEAT1 in gastric cancer.

Methods

The expression of LncRNA NEAT1 was detected in gastric cancer samples and cell lines by real-time PCR. The clinical and prognostic significance of LncRNA NEAT1 in gastric cancer patients was analyzed. Furthermore, the biological function of LncRNA NEAT1 on tumor cell growth and mobility were explored through MTT, colony formation, transwell migration, and invasion assays in vitro. The potential mechanism of LncRNA NEAT1 was identified by Western blot.

Results

LncRNA NEAT1 was overexpressed in gastric cancer tissues and cell lines and corrected with clinical stage, histological type, lymph node metastasis, and distant metastasis. Furthermore, patients with high levels of LncRNA NEAT1 had poorer survival than those with lower levels of LncRNA NEAT1. Univariate and multivariate Cox regression analyses showed that LncRNA NEAT1 overexpression was a poor independent prognostic factor for gastric cancer patients. Moreover, knocking down LncRNA NEAT1 expression significantly suppressed the gastric cancer cell migration and invasion in vitro and regulated EMT-associated proteins expression.

Conclusion

LncRNA NEAT1 plays an important role on gastric cancer tumorigenesis and progression and may act as a potential biomarker for therapeutic strategy and prognostic prediction.

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References

  • Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, Marcos-Gragera R, Stiller C, Azevedo e Silva G, Chen WQ, Ogunbiyi OJ, Rachet B, Soeberg MJ, You H, Matsuda T, Bielska-Lasota M, Storm H, Tucker TC, Coleman MP, Group CW (2015) Global surveillance of cancer survival 1995–2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 385:977–1010

    Article  PubMed  Google Scholar 

  • Chakravarty D, Sboner A, Nair SS, Giannopoulou E, Li R, Hennig S, Mosquera JM, Pauwels J, Park K, Kossai M, MacDonald TY, Fontugne J, Erho N, Vergara IA, Ghadessi M, Davicioni E, Jenkins RB, Palanisamy N, Chen Z, Nakagawa S, Hirose T, Bander NH, Beltran H, Fox AH, Elemento O, Rubin MA (2014) The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun 5:5383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L, He J (2013) The incidences and mortalities of major cancers in China, 2009. Chin J Cancer 32:106–112

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen X, Kong J, Ma Z, Gao S, Feng X (2015) Up regulation of the long non-coding RNA NEAT1 promotes esophageal squamous cell carcinoma cell progression and correlates with poor prognosis. Am J Cancer Res 5:2808–2815

    Article  PubMed  PubMed Central  Google Scholar 

  • Choudhry H, Albukhari A, Morotti M, Haider S, Moralli D, Smythies J, Schodel J, Green CM, Camps C, Buffa F, Ratcliffe P, Ragoussis J, Harris AL, Mole DR (2015) Tumor hypoxia induces nuclear paraspeckle formation through HIF-2alpha dependent transcriptional activation of NEAT1 leading to cancer cell survival. Oncogene 34:4482–4490

    Article  CAS  PubMed  Google Scholar 

  • Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 33:717–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo S, Chen W, Luo Y, Ren F, Zhong T, Rong M, Dang Y, Feng Z, Chen G (2015) Clinical implication of long non-coding RNA NEAT1 expression in hepatocellular carcinoma patients. Int J Clin Exp Pathol 8:5395–5402

    PubMed  PubMed Central  Google Scholar 

  • Guru SC, Agarwal SK, Manickam P, Olufemi SE, Crabtree JS, Weisemann JM, Kester MB, Kim YS, Wang Y, Emmert-Buck MR, Liotta LA, Spiegel AM, Boguski MS, Roe BA, Collins FS, Marx SJ, Burns L, Chandrasekharappa SC (1997) A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus. Genome Res 7:725–735

    CAS  PubMed  PubMed Central  Google Scholar 

  • He C, Jiang B, Ma J, Li Q (2015) Aberrant NEAT1 expression is associated with clinical outcome in high grade glioma patients. APMIS 124(3):169–174

    Article  PubMed  Google Scholar 

  • Hu X, Bao J, Wang Z, Zhang Z, Gu P, Tao F, Cui D, Jiang W (2015) The plasma lncRNA acting as fingerprint in non-small-cell lung cancer. Tumour Biol 9. doi:10.1007/s13277-015-4023-9

  • Li L, Zhang L, Zhang Y, Zhou F (2015a) Increased expression of LncRNA BANCR is associated with clinical progression and poor prognosis in gastric cancer. Biomed Pharmacother 72:109–112

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Shao Y, Zhang X, Zheng T, Miao M, Qin L, Wang B, Ye G, Xiao B, Guo J (2015b) Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumour Biol 36:2007–2012

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Li Y, Chen W, He F, Tan Z, Zheng J, Wang W, Zhao Q, Li J (2015c) NEAT expression is associated with tumor recurrence and unfavorable prognosis in colorectal cancer. Oncotarget 6:27641–27650

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakagawa S, Shimada M, Yanaka K, Mito M, Arai T, Takahashi E, Fujita Y, Fujimori T, Standaert L, Marine JC, Hirose T (2014) The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development 141:4618–4627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Kusunoki M, Boland CR, Goel A (2014) Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis 35:2731–2739

    Article  PubMed  PubMed Central  Google Scholar 

  • Pan LJ, Zhong TF, Tang RX, Li P, Dang YW, Huang SN, Chen G (2015) Upregulation and clinicopathological significance of long non-coding NEAT1 RNA in NSCLC tissues. Asian Pac J Cancer Prev 16:2851–2855

    Article  PubMed  Google Scholar 

  • Pang Q, Ge J, Shao Y, Sun W, Song H, Xia T, Xiao B, Guo J (2014) Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance. Tumour Biol 35:5441–5447

    Article  CAS  PubMed  Google Scholar 

  • Pasechnikov V, Chukov S, Fedorov E, Kikuste I, Leja M (2014) Gastric cancer: prevention, screening and early diagnosis. World J Gastroenterol 20:13842–13862

    Article  PubMed  PubMed Central  Google Scholar 

  • Peng W, Wu G, Fan H, Wu J, Feng J (2015) Long noncoding RNA SPRY4-IT1 predicts poor patient prognosis and promotes tumorigenesis in gastric cancer. Tumour Biol 36:6751–6758

    Article  CAS  PubMed  Google Scholar 

  • Sasaki YT, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci U S A 106:2525–2530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29

    Article  PubMed  Google Scholar 

  • Sun M, Nie FQ, Wang ZX, De W (2016) Involvement of lncRNA dysregulation in gastric cancer. Histol Histopathol 31:33–39

    PubMed  Google Scholar 

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108

    Article  PubMed  Google Scholar 

  • Wang CY, Hua L, Yao KH, Chen JT, Zhang JJ, Hu JH (2015) Long non-coding RNA CCAT2 is up-regulated in gastric cancer and associated with poor prognosis. Int J Clin Exp Pathol 8:779–785

    PubMed  PubMed Central  Google Scholar 

  • Wang J, Su L, Chen X, Li P, Cai Q, Yu B, Liu B, Wu W, Zhu Z (2014) MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF. Biomed Pharmacother 68:557–564

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Yang L, Zhao J, Li C, Nie J, Liu F, Zhuo C, Zheng Y, Li B, Wang Z, Xu Y (2015) Nuclear-enriched abundant transcript 1 as a diagnostic and prognostic biomarker in colorectal cancer. Mol Cancer 14:191

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie M, Nie FQ, Sun M, Xia R, Liu YW, Zhou P, De W, Liu XH (2015) Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition. J Transl Med 13:250

    Article  PubMed  PubMed Central  Google Scholar 

  • You J, Zhang Y, Liu B, Li Y, Fang N, Zu L, Li X, Zhou Q (2014) MicroRNA-449a inhibits cell growth in lung cancer and regulates long noncoding RNA nuclear enriched abundant transcript 1. Indian J Cancer 51(Suppl 3):e77–e81

    Article  PubMed  Google Scholar 

  • Zeng C, Xu Y, Xu L, Yu X, Cheng J, Yang L, Chen S, Li Y (2014) Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells. BMC Cancer 14:693

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Liu Y, Huang G, Cui P, Zhang W, Zhang Y (2015a) Long non-coding RNAs in gastric cancer: versatile mechanisms and potential for clinical translation. Am J Cancer Res 5:907–927

    PubMed  PubMed Central  Google Scholar 

  • Zhao J, Liu Y, Zhang W, Zhou Z, Wu J, Cui P, Zhang Y, Huang G (2015b) Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer. Cell Cycle 14:3112–3123

    Article  PubMed  Google Scholar 

  • Zhen L, Yun-Hui L, Hong-Yu D, Jun M, Yi-Long Y (2015) Long noncoding RNA NEAT1 promotes glioma pathogenesis by regulating miR-449b-5p/c-Met axis. Tumour Biol 5. doi:10.1007/s13277-015-3843-y

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Jining No. 1 People’s Hospital, No. 6, Jiankang Road, Jining City, 272011, Shandong Province, People’s Republic of China

    Jing-wei Fu & Ying Kong

  2. Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, No. 440, Jiyan Road, Jinan City, 250117, Shandong Province, People’s Republic of China

    Xu Sun

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  1. Jing-wei Fu
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  2. Ying Kong
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  3. Xu Sun
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Correspondence to Xu Sun.

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Jing-wei Fu and Ying Kong are co-first authors.

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Fu, Jw., Kong, Y. & Sun, X. Long noncoding RNA NEAT1 is an unfavorable prognostic factor and regulates migration and invasion in gastric cancer. J Cancer Res Clin Oncol 142, 1571–1579 (2016). https://doi.org/10.1007/s00432-016-2152-1

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  • DOI: https://doi.org/10.1007/s00432-016-2152-1

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